The conducted study is directed towards enhancements in performance assessment of highway bridges under a wide range of earthquake input shaking scenarios. Seismic response of the superstructure is highly influenced by the global bridge-ground characteristics as an integral system. Therefore, nonlinear representation of the bridge deck, columns, abutments, and foundation response are to be integrated within a unified framework. On this basis, a performance-based earthquake engineering (PBEE) framework was extended and utilized to estimate the post-earthquake loss. To facilitate systematic execution of this analysis framework, a graphical user-interface was further developed and employed. For calibration purposes, a Finite Element (FE) model of an existing large heavily instrumented bridge system at Eureka, California (Samoa Channel Bridge) was developed. Calibration was undertaken based on the recorded earthquake response. Numerical simulations of the bridge model under seismic loading conditions were conducted. Simulation results show that the recorded data provide valuable insights to understand the seismic bridge response and to reliably estimate the damage. Using a practice-oriented pushover procedure, the response of a bridge subjected to liquefaction-induced lateral spreading was investigated. The analysis framework and representative results are presented, where the abutment lateral slope displacement is resisted by the entire bridge configuration. Permanent ground deformation induces longitudinal displacement on the abutment and consequently the entire bridge system. As such, the response of the bridge and its pile foundations were investigated and correlated with the imposed lateral spreading displacement. Overall, the novel contributions and findings are summarized as follows: (1) A bridge-ground seismic response computational analysis tool was further developed for routine practical applications; (2) In this tool, a PBEE framework was extended to handle multi-span bridge-ground systems within an integrated simulation environment; (3) Calibrated by recorded earthquake response, a framework was implemented for a representative large instrumented bridge-ground system in California to illustrate the involved response mechanisms and PBEE outcomes; (4) For response under lateral spreading considerations, a global bridge-ground systematic analysis framework was proposed and developed; (5) Patterned after an existing bridge in California, the framework was implemented with parametric studies addressing the procedure assumptions and potential retrofit bridge configurations.